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Testing for Immunologic Implantation Dysfunction (IID): Who Should be Tested, Where Should Testing be Done and How should results be interpreted?

by Dr. Geoffrey Sher on January 20, 2017

Unless tests for immunologic implantation dysfunction (IID) immunologic implantation dysfunction are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of Reproductive Immunology Reference Laboratories in the world that can perform all these tests with optimal reliability….and most are in the U.S.A ( I personally recommend Reproductive Immunology Associates -RIA, located in Van Nuys, CA and Reprosource in Boston, MA, preferentially).  Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by sub optimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.

Who Should Undergo IID testing?

When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:

  • A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
  • A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
  • “Unexplained” infertility
  • Recurrent pregnancy loss (RPL)
  • A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
  • Unexplained IVF failure
  • “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby

What Parameters should be tested?

In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.

The parameters that require measurement include:

o             For Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are:  a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6,  Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing  the required elements with a sufficient degree of  sensitivity and specificity (in my opinion).

o             For Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).

How should results be interpreted?

Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample  in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit.  Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.

There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL.  However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.

Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.

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  • Michelle - August 14, 2017 reply

    6 years ago I had a miscarriage at 10 weeks. I’ve had two ivf transfers both with slightly raised hcg, endo lining 7-8mm, implantation failure. I’ve tried naturally with no luck. I have been checked and don’t have any specific diagnosed condition endo, pcos, fullopian tubes not blocked, etc.. I have raised NKC cells 10% by test result. I am looking to give it one last shot for a baby, I’m 44 and understand age is an issue. I have been advised by a fert specialist in Australia to do AACEP. She also advised I check you site on the website…so here I am. I’ve watched some of your videos very informative thank you for sharing. If we do this protocol do you suggest we also use immune suppressant drugs to address my nk cell issue and is there anything else you might recommend for my circumstance. Thank you. Michelle

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - August 14, 2017 reply

    First you need to be certain that the the NK cells are “activated” and what the cause is. The concentration in the blood is irrelevant. You need the K-562 target cell test (blood test) and/or and endometrial biopsy for cytokines. If the NKa are raised, you should then exclude an alloimmune cause by you and your partner being tested for DQalpha/ HLA genetic matching. I do not think there is a lab in Australia that can do these tests well. You would need to contact and then send your blood to the USA. I use Reprosource in Boston, MA. You can google them.

    Good luck!

    Geoff Sher

  • Joanna Troccoli - July 21, 2017 reply

    Hi Dr.Sher
    I am in need of some help. I have lost 5 pregnancies in the past year since may 2016. May I got pregnant with IUI , beta started at 12 … continued to double until bleed and loss at 5 1/2 weeks, July chemical pregnancy through iui , September first IVF pregnant lost baby at 10 weeks , chromosome testing normal , January frozen transfer negative , march fresh ivf chemical with beta of 3, now July frozen transfer of PGD tested normal embryo most likely experiencing chemical as low starting beta. This cycle we did intralipid , lovenox, metformin, baby aspirin , predisone, ….. I did the immune testing with dr.braverman and it’s something about my body attacking the antibodies in the embryo? I have one PGD tested normal embryo left and I don’t know where to go from here. I am with your clinic in NY which has been awesome but I am still without baby and 5 cycles in. Is it worth me trying again or does surrogacy seem to be my only option ? I’m desperate thank you dr.sher ….. by the way I have one child a boy 3 1/2 years old conceived naturally

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 21, 2017 reply

    I really think there would be an advantage in us talking!

    When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
    Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
    • Early pregnancy loss (first trimester)
    • Late pregnancy loss (after the first trimester)
    • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
    • Early pregnancy losses usually occur sporadically (are not repetitive).
    In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
    Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
    There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
    Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
    Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
    1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
    • Inadequate thickening of the uterine lining
    • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
    • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
    • Deficient blood flow to the uterine lining (thin uterine lining).
    • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
    • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
    2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

    IMMUNOLOGIC IMPLANTATION DYSFUNCTION
    Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
    But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
    Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
    Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

    Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
    However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
    DIAGNOSING THE CAUSE OF RPL
    In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
    Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

    • Karyotyping (chromosome analysis) both prospective parents
    • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
    • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
    • Hysterosalpingogram (dye X-ray test)
    • Hysteroscopic evaluation of the uterine cavity
    • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
    • Immunologic testing to include:
    a) Antiphospholipid antibody (APA) panel
    b) Antinuclear antibody (ANA) panel
    c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
    d) Reproductive immunophenotype
    e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
    f) Alloimmune testing of both the male and female partners
    TREATMENT OF RPL
    Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
    Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
    Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

    Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
    Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
    The Use of IVF in the Treatment of RPL
    In the following circumstances, IVF is the preferred option:
    1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
    2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
    The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
    Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
    There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
    The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    ANNOUNCEMENTS:
    1. About my Retirement by mid-2018:
    After > 30 years in the field of Assisted Reproduction (AR), the time is approaching for my retirement. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
    If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

    2. The 4th edition of my newest book ,
    “In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    joanna troccoli - July 24, 2017 reply

    I reached out to Judy and hopefully can talk to you at your earliest convenience. I hope to be able to send over my immune report and bloodwork findings as well so that we can go over it when we speak. Thank you so much

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 24, 2017 reply

    I look forward to it!

    Geoff Sher

    joanna troccoli - July 25, 2017

    Hi Dr. Sher, I tried emailing, texting, and calling and have not heard back yet from Judy…Does it usually take a little while to get a response? Very anxious to get a consult with you before we use our finally PGD tested embryo. Thank you

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 26, 2017

    I will alert Julie!. This is most unusual as she is usually most responsive!

    Geoff Sher

    joanna troccoli - July 26, 2017

    thank you so much! i though unusual too but I tried all three forms of communication and nothing .Thank you so much!!!! really can’t wait to talk. my email is joannamehrer@gmail.com if she needs it.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 26, 2017

    You are most welcome Joanna!

    Geoff Sher

  • Anne - April 28, 2017 reply

    You natural killer cell activity level is 32%. What are my treatment options for getting pregnant naturally or through ivf.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 28, 2017 reply

    32% NKa by the K-562 target cell test is probably as high as I have ever seen. I think we should talk.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • :
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

    I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Neha Ohri - April 17, 2017 reply

    Dear Dr Sher,

    We have been reading your blogs & watching your podcasts with great interest and we are really hoping that you can offer us some advice/guidance in the way forward for our treatment to achieve our goal in having a healthy baby.

    Briefly our current situation is as follows:-

    I am 38yrs old (DOB: 22/07/1978) and am a Duchenne Muscular Dystrophy (DMD) Carrier. My husband is 42yrs old (DOB: 04/08/1978).

    Past History
    – June 2010: Miscarriage after 5weeks.
    – 3 further years of trying to conceive again naturally but not being able to do so.
    – Jan 2014: IVF + PGD Cycle 1 – Resulted in 1 normal PGD 5 day hatching blastocyst being available and a frozen embryo transfer not implanting.
    – Oct 2014: IVF + PGD Cycle 2 – Resulted in 1 normal PGD 5 day hatching blastocyst being available and a fresh embryo transfer not implanting.
    – March 2015: IVF + PGD Cycle 3 – Resulted in no embryos being available for transfer.
    – Nov 2015: IVF ERA + PGD + PGS Cycle 4 – Resulted in 1 normal PGD + Normal PGS 5 day hatching blastocyst being available and a frozen embryo transfer not implanting.

    After overcoming the first hurdle of having blastocysts available to transfer following a PGD test for DMD we were disheartened by the fact that we did not achieve implantation despite having even done a PGS test to ensure our latest transfer was a chromosomally normal embryo and the transfer took place when the endometrium was receptive (ERA Test).

    So we decided to further investigate why implantation was not occurring and decided to perform immunology blood tests & an endometrium NK cell biopsy at the Double Helix Immunology Centre in New Delhi.

    The results of these tests was as follows:-

    Blood Tests
    > Th 1 Type Cytokine Estimation (TNF-a) – Result 984.591 pg/ml (Normal Range: 600 pg/ml)
    > CD3 (Pan T Cell) – 82.0% (Normal Range: 63% – 86%)
    > CD19 (B Cells) – 7.7% (Normal Range: 3% – 8%)
    > CD56+CD16+Cell – 11% (Normal Range: 3% – 12%)
    > CD56 Cells – 19.2% (Normal Range: 3% – 12%)

    Endometrium NK Cells Biopsy
    > Tumor Necrosis Factor – a (TNF-a) activity – Negative
    > Natural Killer (NK) Cells activity – Positive
    > Integrins – Negative
    > Progesterone Receptor – Postive

    We were advised that these results showed that I had a high level of NK cell activity and that this may be the cause of repeated implantation failure and would need to be tackled during any further embryo transfers.

    We have since carried out 3 further IVF + PGD + PGS pooling cycles and have now banked 3 PGD clear and chromosomally normal blastocysts which are available for FET transfer.

    Our IVF doctor has recommended the following protocol for transfer:-
    – 75mg Aspirn & CoQ10 100mg & Calcimax & Pregnacare
    – IVIG 5g infusion now & another 5g infusion after 21days & then again following a positive pregnancy test
    – On day one of period to take 5mg Progynova (13days) & 10mg Wysolone (Prednisone)
    – On day 13 to take 400mg of Susten (Progesterone) for 5 days as per my ERA protocol (HRT P + 5)

    What advice/guidance can you give us with regards to the protocol being suggested by the IVF doctor and do you feel that the dosage of IVIG & Prednisone is sufficient and being given at the correct time to suppress active NK cells prior to and after embryo transfer?
    Is there any benefit in having further blood tests to evaluate NK cells in perhiphal blood maybe after 7 days post my first IVIG infusion to see if the levels have indeed been supressed?
    Is IVIg or IL more effective in suppressing high levels of active NK cells? And also does acupuncture help in bringing these levels down?

    You eagerly look forward to your reply.

    Kindest Regards

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 17, 2017 reply

    I agree that it sounds as if you have NKa+. However: 1) in my opinion, 5G of IVIG is placebo and will likely have no effect. Tf IVIG is to be used, the dosage is in my opinion, 40G infused 10-14 days prior to ET and again as soon as the beta hCG test is +ve. It should be combined with steroid therapy. However, I no longer prescribe IVIG since intralipid (IL) therapy is equally effective, much less expensive, and associated with far less side effects or risk. It too is combined with steroid therapy.

    However, this treatment is effective for autoimmune implantation dysfunction. It needs to be adjusted for alloimmune implantation dysfunction. Thus the differential diagnosis needs first to be established….see below.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

    I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Mia - March 5, 2017 reply

    Dear Dr. Sher – what would you recommend if I can not tolerate steroids and it is now not medically recommended? Will IVIG or IL even be effective or a waste of time? I have had difficulties with implantation with own eggs (2 transfers) and donor eggs (1 transfer). I also have endometriosis, a small intramural fibroid, elevated NK cells activity, and have had issues with my thyroid. I did have a natural conception with a boy while taking a break from IVF. The pregnancy began while I was only on progesterone for luteal phase only and the pregnancy was very challenging from the beginning with cramping and light bleeding. It ultimately ended in a stillbirth at 24 weeks – the child autopsy was normal as was the karyotype. I will also mention that my thyroid treatment has been problematic – I usually stay within normal ranges until I take hormones and then I quickly go subclinical hypothyroid (as I did with last FET with donor eggs). Over a period of time with thyroid replacement I can swing to hyperthyroid and antithyroid antibodies can develop. Once I stop medication it can take a while but thyroid levels normalize and antibodies are to detected – but then it starts all over again with hormones, especially when using BCP or lupron.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 5, 2017 reply

    Hi Mia,

    Frankly, in my opinion, steroid supplementation is a very important part of the comprehensive treatment of immunologic implantation dysfunction. I find it hard to accept that steroids (oral versus parenteral) would not be tolerated. After all, everyone produces them endogenously. You would simply need to tailor the product and the administration to your needs. If you cannot golerate steroids orally, it can be injected.

    Geoff Sher

  • Natalie - February 28, 2017 reply

    Hi, i had three failed pgs FET with no explanation since i have done era test, water test, 1 ml polyp removal, hsg test all normal. My re stated it was a male factor but since we have the embryos and its still failing im thinking its my uterus killing the embryos, she also had me take doxycline for 2 weeks prior to FET along with estrace, aspiring and progesterone shots and 2 days of progesterone vaginal pills. How can i test for IID? Is it a blood test? Do you think this can be reason for the failure? She had also Rx me two sets of antibiotics but after the fitst dose they made me sick so i stopped and went back to doxy. Now we only have two frozen embryos left. Please help

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 28, 2017 reply

    It is indeed possible that IID could be the reason for failure.

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

    I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Carla - February 11, 2017 reply

    Dear Dr Sher,

    In last few days I have read 80% of your blogs and I finally feel I am not alone and see some light at the end of the tunnel. There is Pacific Ocean between us otherwise I would already be in front of your office. Thank you for all of the support you are giving to us that are dealing with this complex issue, while just wanting to start a family and live a fruitful simple life.

    I am having regular ovulatory 32-35 days cycles with prolonged duration (up to 2 weeks), endometriosis, positive thyroid antibodies (over 1300) without therapy as hormones are in normal range, PAI-1 (4G/5G): homozygote 5G, positive ANA (1:640), partial HLA match with my husband in HLA-A,HLA-B,HLA-C,HLA-DRB1,HLA-DQA1 (me: 05:05, n.a. / husband: 01:04, 05:05),HLA-DQB1,HLA-DPB1.
    In 2009 I had autoimmune thrombocytopenia, cured with IVIG & corticosteroids (Medrol) within 3,5 months. Since then, no issues with that.
    Other tests done were normal: APTV, LAC, Protein S, anticardiolipin antibodies IgG & IgM, anti-beta-2-glycoprotein IgG & IgM, factor V Leiden, factor II prothrombin, MTHFR, antithrombin III, Protein C, homocysteine, karyotype (both mine and husband’s), TSH, T4, T3, AMH (22.7), LH, FSH, testosterone, estradiol, prolactin, DHEAS, androstenedione, SHBG.
    I am 31 & my husband is 36 (spermiogram from 2014 was normal). We do not have autoimmune diseases in family history besides minor thyroid issues, without necessary treatment. Also, all of my close relatives, including my sister did not have fertility problems. I have no uterine abnormalities & I have 7-12 mm uterine lining at ovulation.

    With help of regular foliculometry I had 3 pregnancies during last 12 months: 1. Missed abortion (D&C at 10w, CRL 30 mm, PHD: residua placentae, medicaments: only preventive oral progesterone till 6w when stopped due to migraine) 2. Chemical pregnancy 3. Missed abortion (D&C at 7w6d, CRL 5 mm, PHD: in progress, medicaments: only preventive vaginal utrogestan).
    Next week I am doing NK cells test (only quantitate test available). I would very much appreciate your respectful opinion if I would be a good candidate for IVIG/IL/steroid therapy jointly with IVF procedure & PGD with 1 embryo transfer (as I see I might have both autoimmune & alloimmune implantation dysfunction).

    Many thanks,
    Carla

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 11, 2017 reply

    I am persuaded that you in fact likely have a significant immunologic implantation dysfunction (IID). You already have a partial DQ alpha match with your husband and I strongly suspect you will have activation of NK cells (NKa) . The two go hand in hand to cause an alloimmune implantation dysfunction which I strongly suspect lies at the root of your reproductive dysfunction. I must however caution you about the testing for NKa and its interpretation.

    There are several methods by which NK cell activation (cytotoxicity) can be assessed in the laboratory. Methods such as immunohistochemical assessment of uterine NK cells and/or TH-1 and TH-2 cytokines have been used with some success. However, use of the K-562 target cell test remains the gold standard. With this test, NK cells are isolated from the woman’s blood using Flow Cytometry and are incubated in the presence of specific “target cells”. These are then incubated together. The percentage (%) of “target cells” killed through exposure to NKa/CTL-TH1 cytokines is then quantified.

    Currently, there are less than a half dozen Reproductive Immunology Reference Laboratories in the U.S.A that are capable of performing the K-562 Target cell test reliably. I have for 20 + years been working with Reproductive Immunology Associates (RIA) in Van Nuys, CA and preferentially recommend them to my patients.

    Since yours is likely an alloimmune problem due to a partial DQA alpha match (plus NKa+), onnly one out of two blastocysts will be non-matching and capable of propagating a viable pregnancy. Simply stated , even with IL/steroids, a matching embryo is highly unlikely to take. Since one in two embryos will match and be likely to activate NK cells, it would in my opinion be unwise to transfer >1 embryo at a time since if 2 are transferred and one activates local NK cells, it could “muddy the waters for both”. Moreover, since each transferred embryo thus would have half the usual chance of implanting successfully, it would in my opinion be wise to identify those embryos that are most “competent” through karyotyping (PGS).

    There exist a pervasive but blatant misconception on the part of many, that the addition of IL/IVIG can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells. This process takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, it is in reality would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory and by that time it would be far too late to be of practical advantage.

    Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus it should be infused several days prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers Should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

    I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Carla - June 23, 2017 reply

    Dear Dr Sher,
    I am reffering to your reply from February 11th, 2017.
    Thank you for the valuable comments and advise how to proceed. Since my last post, I have found out that my last loss was due to partial molar pregnancy (DC preformed and luckily no further complications with it). Besides, my NK cells blood results came at 65%. After that I had another chemical pregnancy (I was taking progesterone, baby aspiring, folic acid, euthyrox 25 mg and decotrin 5 mg (steriods) from 13 dpo ultrasound where gestational ring was visible). So till now, I had 4 pregnancy losses (1st missed abortion, 2nd chemical pregnancy, 3rd partial molar pregnancy 4th chemical pregnancy). My doctor has suggested to try with IVF in September but honestly I do not see how this can help possible immunological issues as there would be no PGS nor other advanced testing available. IVIG might be available but due to high costs doctor does not recommend it for now but sees it as a last resort (lipid therapy also not available). Currently, I am looking for other options and would be interested to have guidance by reproductive immunology expert. However, I am far away for in person treatment I would like to understand do you maybe have affiliate offices in Europe where treatment can be done with your guidance, and also if blood specimen for the necessary blood work can be sent to you somehow. I would be happy to book consultation if you are working with dislocated patients as well.
    Thank you Dr Share, so much!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 23, 2017 reply

    Hi Carla,

    I really think we should talk!

    Geoff Sher

    Carla - June 24, 2017

    Thank you. I will book a consultation immediately.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 24, 2017

    Copy!

    Geoff Sher

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